Sickle cell disease (SCD) is an inherited anemia in which formation of hemoglobin polymer causes destruction of the red blood cells, a process called hemolysis. SCD is recognized as a significant global public health problem. Over 90% of the 300,000 annual births with SCD occur in resource-poor countries, and most of the affected children die from preventable causes. Thus, there exists an urgent need for technologies to screen infants for SCD so that appropriate health care measures can be initiated. The aim of this proposal is to develop a robust point-of-care diagnostic system based upon measurement of breath carbon monoxide (CO) level. CO in exhaled breath is largely derived from the oxygen-dependent catabolism of heme during destruction of red blood cells, a process accelerated in SCD. Capnia has a device, CoSense, which is currently cleared by the FDA for End-Tidal Carbon Monoxide (ETCO) monitoring. The use of end-tidal breath samples allows the measurement of exhaled CO in young children who cannot provide a forced breath sample. A recent preliminary study demonstrated that ETCO levels measured by CoSense were 6-fold higher in SCD than the controls. Therefore, CoSense, as a screening tool, may be extremely helpful in identifying infants with SCD in resource-poor countries where newborn screening is not available. In Phase I of the SBIR proposal, the current device will be modified to extend its temperature operating range.